Pharmaceutical Tablet Formulation

Tablet Evaluations

• Tablets are a unit dosage form, easy to handle, store, and dispense.
• Manufacturing cost is lower compared to other dosage forms.
• Release profile is easily controlled and manipulated.
• Some drugs resist compression, not ideal for masking bad taste or smell.
• Difficulty formulating drugs with poor wetting properties.
• Some drugs degrade when taken orally.

Types of Tablets

• Various types, including vaginal, cough lozenges, and enteric-coated aspirin.
• Visual examples are provided in the slides.

Granulation

• Fine powder drugs generally have poor flow properties.
• Granules have better flowability and compressibility than individual ingredients.
• Granulation ensures consistent API spread in the formulation.

Compression

• The final step in tablet formulation.
• Requires variables beyond the scope of the course.
• Diagram of the compression process is shown.

Tablet Evaluation

• General appearance is critical for consumer acceptance, lot-to-lot uniformity, tablet-to-tablet uniformity, and trouble-free manufacturing.
• General appearance involves measuring factors like size, shape, color, odor, taste, texture, physical flaws, consistency, and legibility of markings

Unique Identification Markings

• Used for quick product identity.
• Information typically includes company name, product code, potency.
• Tablet prints must be clear and flaw-free.
• Examples of different tablet prints are given.

Organoleptic Properties

• Color is vital for rapid identification and consumer acceptance, must be uniform.
• Mottling (non-uniform color) may negatively affect patient acceptance.
• Odor can indicate stability problems, as seen in aspirin degradation.
• Taste is important, especially for chewable tablets.
• Visual flaws like chips, cracks, or foreign bodies, affect patient acceptance.
• Surface texture (smooth/rough) and appearance (shiny/dull) are also assessed.

Size and Shape

• Tablet shape and diameter are determined by the die shape.
• Tablet thickness is the only dimensional variable related to the process.
• Thickness should be consistent across batches.
• Inconsistent thickness can indicate content uniformity problems, affect patient acceptance, and lead to packaging issues.
• Thickness is measured with a micrometer caliper.
• Thickness variation should not exceed ± 5%.

Tablet Hardness (Non-Official)

• Tablets must withstand mechanical stress during manufacturing, packaging, shipping, and handling.
• Tablet hardness is related to disintegration time.
• Hardness can be varied by die filling, compression force, and binder amount.
• Testing involves measuring the force to break a tablet.

Tablet Friability (Official USP)

• Hardness is not the sole measure of good tablets; friability is also needed.
• A friability test evaluates a tablet's resistance to mechanical stress.
• Tablets that crumble or fragment when handled lack consumer acceptance.
• Roche friabilator, a laboratory device used for the test.
• Conventional compressed tablets should lose less than 1% of their weight.

Drug Content and Release

• A physically sound tablet may not always deliver the desired effects.
• Measuring drug content per tablet and batch is essential.
• Measuring a tablet's ability to release the drug is important.
• Official USP tests include weight variation, content uniformity, disintegration, and dissolution testing.

Weight Variation (Official USP)

• Weight of tablets must be within USP weight variation limits.
• Factors leading to weight variation include poor flow and machine setup.

Content Uniformity Test (Official USP)

• Ensures active pharmaceutical ingredients are evenly distributed within the tablet, within the limit.

Disintegration Test (Official USP)

• Measures the time it takes for a tablet to break down into smaller particles.
• Usually, tablet disintegration should happen in under 30 minutes.
• Enteric-coated tablets need longer disintegration time (at least 1 hour).

Dissolution Test (Official USP)

• Measures how quickly the drug dissolves to be absorbed by body.
• The drug in solution is readily absorbed.
• Dissolution results are plotted as % release versus time.
• A simulation apparatus, USP dissolution apparatus is commonly used.

Importance of Dissolution Testing

• Guides formulation and product optimization.
• Monitors manufacturing quality.
• Ensures bioequivalence of batches.
• Facilitates regulatory approval for marketing.

Processing Problems

• Final tablet formulation can undergo problems after being compressed, packaged, shipped, stored, and handled.
• Problems can arise from manufacturing, excipients, or both.

Problems Related to Tablet Processing

• Capping: partial or complete separation of the tablet's top or bottom crown from the main body.
• Lamination: complete separation into multiple layers.
• These may occur immediately after compression or hours/days later.
• Capping/lamination issues are related to air entrapment during compression or deformation properties during compression.

Causes of Capping and Lamination

• Air entrapment during compression.
• Deformational properties of the formulation during or immediately after compression.
• Incorrect excipient choices especially the binder.
• Granule dryness can cause cohesion issues.
• Poor compression machine setup.

Deformational Changes (Causes of Capping and Lamination)

• Compaction creates wall pressure higher than the elastic recovery from pressure removal.
• This leads to cracks, and fractures upon decompression.
• Portion of the compact expands causing shear stress.
• Tablets that don't fracture have stress relaxation; therefore, fracture happens later over time.

Problems related to Tablet Processing

• Over compression
• Tablet thickness can cause binding problems.

Solution for Capping and Lamination

• Slowing compression speed and reducing pressure allows air escape.
• Pre-compression steps with gentler force pre-form the tablet.
• Selecting the correct excipients.
• Using another tablet shape, like a flat-end, has lower fracture tendency.
• Deep concave punch shape that expands the tablet surface may cap the tablet.

Problems Related to Tablet Processing

• Cracking, due to rapid tablet expansion after compression, or poor granulation (dryness), or cold environment.
• Solution: improve tablet formulation, and optimize binder usage during granulation.

Problems Related to Excipients

• Chipping: breaking edges due to poor particle flow (lack of lubrication).
• Sticking: tablet material sticking to die/punch faces or the machine.
• Picking: small portion of tablet surface sticking to the punch faces.
• Mottling: unequal color distribution related to use of dyes or degradation.

Solutions (Excipient Problems)

• Adjust lubricant amount.
• Improve granule drying.
• Properly designing lettering depth and position.
• Adjust solvent system/ properly granulate the dye.
• Avoid large chunks of dye.

Other Problems

• Weight variation: Tablets with weights outside the USP limits.
  • Die filling problems: Variations in lower punch length.
  • Granule size and distribution variations.
  • Poor flow: Insufficient lubricant.
  • Poor hooper design.
• Poor mixing: Insufficient lubricant or glidant distribution.
• Double impression: Punch rotating slightly during compression.
• Uneven breakage: Caused by coarse granules and improper mixing.

This quiz covers the essential aspects of pharmaceutical tablet formulation, including the types of tablets, granulation, and compression processes. Understanding tablet evaluation and characteristics is crucial for ensuring consumer acceptance and effective drug delivery. Test your knowledge on the manufacturing and formulation of tablets.